Identification of genetic and metabolomic markers influencing dystonia

鉴定影响肌张力障碍的遗传和代谢组学标记

基本信息

批准号：
9262303
负责人：
HYDER A JINNAH
金额：
$ 15.6万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-15 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9262303
关键词：
Address Adult Affect Bioinformatics Biological Blepharospasm Body Regions Candidate Disease Gene Cells Cervical Dystonia Clinical Collection Data Development Diagnosis Dystonia Environment Environmental Exposure Environmental Risk Factor Genes Genetic Genetic Predisposition to Disease Genetic Variation Genetic study Genomics High Prevalence Human Individual Knowledge Light Link Measures Mediator of activation protein Medical Metabolic Metabolism Molecular Movement Disorders Pathway interactions Patients Phenotype Physiological Plant Roots Prevention Risk Risk Factors Role Sample Size Sampling Source Surrogate Markers Syndrome System Technology Testing Twin Multiple Birth Variant accurate diagnosis biological systems clinical practice effective therapy falls genetic predictors genetic variant genome wide association study insight metabolome metabolomics non-genetic peripheral blood public health relevance rare variant risk variant small molecule

项目摘要

DESCRIPTION (provided by applicant): As the third most common movement disorder, dystonias collectively affect more than 2 million people worldwide. Despite their high prevalence, their biological roots are largely unknown. Both genetic and environmental influences are suggested in familial studies, however, no specific genetic variants or environmental factors are responsible for a significant proportion of identified cases. Metabolomic profile of peripheral blood can be influenced by environmental and genetic factors, as well as physiological condition of an individual. Studying the metabolomic profile is an important component to understand the biological systems linking the environment, genomics and the development of dystonias. Molecular and system understanding of the dystonias would enhance the clinical practice of accurate diagnosis and effective treatment. Previous genome-wide association studies of the dystonias were limited by smaller sample size and lack of coverage of rare variants. No metabolomic study of the dystonias has been conducted to investigate the role of small molecules. In this study, we will use a high-throughput genomic and metabolomic approach to effectively investigate relationships between over 1.7 million genetic variations and over 20,000 metabolomic features. We will conduct targeted analyses of candidate genes, as well as agnostic searches for any genomic and metabolomic associations with the dystonias in the largest sample of dystonia patients available in the US.

描述（由申请人提供）：作为第三种最常见的运动障碍，肌张力障碍在全球范围内影响了超过 200 万人，但家族研究表明其生物学根源在很大程度上尚不清楚。没有特定的遗传变异或环境因素导致很大一部分已识别的病例，外周血的代谢组学特征可能受到环境和遗传因素的影响，并且研究个体的代谢组学特征是了解的重要组成部分。这将环境、基因组学和肌张力障碍的发展联系起来的生物系统将增强准确诊断和有效治疗的临床实践，此前对肌张力障碍的全基因组关联研究受到样本量较小和缺乏的限制。尚未对肌张力障碍进行代谢组学研究来研究小分子的作用。在这项研究中，我们将使用高通量基因组和代谢组学方法来有效研究 1.7 以上之间的关系。我们将对候选基因进行有针对性的分析，并在美国最大的肌张力障碍患者遗传样本中寻找与肌张力障碍的任何基因组和代谢组学关联。